This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.
Objective. To test the hypothesis of an association between a polymorphism in the matrix metalloproteinase 3 (MMP-3) gene promoter and the susceptibility, severity, and progression of rheumatoid arthritis (RA), and to further document the association between HLA-DRB1 alleles encoding the shared epitope (SE) and the severity and progression of RA.Methods. Patients with early RA (n ؍ 103) were included in this prospective study. A total radiographic damage score (TDS; by the Sharp/van der Heijde method) was used to quantify RA severity at baseline and after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP-3 gene promoter was analyzed using fluorescence-based polymerase chain reaction (PCR). HLA-DRB1 genotyping was performed using PCR methods. Control subjects (n ؍ 127) were unrelated healthy individuals.Results. MMP-3 allele carriage rates and allele and genotype frequencies did not differ between patients and controls. The MMP-3 6A/6A genotype was associated with the highest TDS both at baseline and after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. The DRB1 SE؉/؉ genotype was associated with the highest TDS after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. Patients homozygous for MMP-3 6A and DRB1 SE had the highest progression of the TDS.Conclusion. This study provides the first evidence of an association between a polymorphism in the MMP-3 gene promoter and the severity and progression of RA, but not RA susceptibility. Investigation of this polymorphism could be combined with that of DRB1 gene polymorphism to improve the predictive accuracy and management strategy in early RA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.